There are a variety of chronic ocular disorders, which, if untreated, may lead to partial or even complete vision loss. One prominent chronic ocular disorder is age-related macular degeneration, which is the leading cause of blindness amongst elderly Americans affecting a third of patients aged 75 years and older (Fine et al. (2000) NEW ENGL. J. MED. 342:483-492). There are two forms of age-related macular degeneration, a wet form, which is associated with the formation of neovasculature in the choroid (also known as the neovascular form of age-related macular degeneration), and a dry form, which is not associated with the formation of choroidal neovasculaturization. The wet form accounts for approximately 90% of the severe vision loss associated with age-related macular degeneration.
Currently, treatment of the dry form of age-related macular degeneration includes administration of antioxidant vitamins and/or zinc. Treatment of the wet form of age-related macular degeneration, however, has proved to be more difficult. Currently, two separate methods have been approved in the United States of America for treating the wet form of age-related macular degeneration. These include laser photocoagulation and photodynamic therapy using a benzoporphyrin derivative photosensitizer. During laser photocoagulation, thermal laser light is used to heat and photocoagulate the neovasculature of the choroid. A problem associated with this approach is that the laser light must pass through the photoreceptor cells of the retina in order to photocoagulate the blood vessels in the underlying choroid. As a result, this treatment destroys the photoreceptor cells of the retina creating blind spots with associated vision loss. During photodynamic therapy, a benzoporphyrin derivative photosensitizer is administered to the individual to be treated. Once the photosensitizer accumulates in the choroidal neovasculature, non-thermal light from a laser is applied to the region to be treated, which activates the photosensitizer in that region. The activated photosensitizer generates free radicals that damage the vasculature in the vicinity of the photosensitizer (see, U.S. Pat. Nos. 5,798,349 and 6,225,303). This approach is more selective than laser photocoagulation and is less likely to result in blind spots. Under certain circumstances, this treatment has been found to restore vision in patients afflicted with the disorder (see, U.S. Pat. Nos. 5,756,541 and 5,910,510).
Another prominent chronic ocular disorder is uveitis. Uveitis is an inflammatory eye disorder and includes inflammation of the uveal tract, the vascular coat of the eye composed of the iris, ciliary body and choroid. While the ultimate goal of inflammation is to repair the initial cause of cell injury, inflammation can also cause harm to cells. This harm is thought to be caused by leukocytes which migrate from the microcirculation and accumulate and secrete cytokines at the site of accumulation. Among the complications associated with the inflammatory process in uveitis are glaucoma, lens opacification, retinal detachments and cystoid macular edema. All these can cause permanent vision loss.
Available treatments for uveitis are limited. Corticosteroids are the main drugs used for its treatment but they have numerous ocular (cataract and secondary glaucoma) and non-ocular adverse effects. Prolonged systemic steroid use can suppress musculoskeletal growth, cause impaired wound healing and result in increased susceptibility to infections. Cycloplegics are used for the alleviation of pain but can have adverse effects including photophobia and blurred vision. Thus, there is still an ongoing need for methods of preventing the onset of chronic ocular disorders, and once established, the treatment of such a disorder.